Fabrication of a high resolution biological molecule detection device with aluminum electrical conductors

ABSTRACT

The present invention relates to a method of manufacturing a detection device which involves providing a substrate having a layer of aluminum and a first layer of photosensitive material. Next, the substrate is subjected to a first level photolithography treatment to produce an aluminum electrical conductor containing conductive fingers with spaces between them. Finally, biological probes are attached to the conductive fingers under conditions effective to form a gap between the biological probes on the spaced apart conductive fingers. As a result, a target molecule, if present in a sample, can bind to a pair of the biological probes on the spaced apart conductive fingers to bridge the gap between the biological probes, allowing detection of the target molecule.

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 60/332,282, filed Nov. 21, 2001, which is herebyincorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to methods of fabricating a device for thedetection of target biological molecules from samples.

BACKGROUND OF THE INVENTION

For the analysis and testing of nucleic acid molecules, amplification ofa small amount of nucleic acid molecules, isolation of the amplifiednucleic acid fragments, and other procedures are necessary. Thepolymerase chain reaction method is widely used for the amplification ofnucleic acid molecules, in which an extremely small number of nucleicacid molecules or fragments can be multiplied by several orders ofmagnitude to provide detectable amounts of material. On the other hand,isolation and detection of particular nucleic acid molecules in amixture requires a nucleic acid sequencer and fragment analyzer, inwhich gel electrophoresis and fluorescence detection are combined.However, electrophoresis becomes very labor-intensive as the number ofsamples or test items increases. For this reason, a simpler method ofanalysis using DNA oligonucleotide probes is becoming popular. In thismethod, many kinds of oligonucleotide probes are immobilized on thesurface of a solid to make a probe array. When contacted with a sample,only nucleic acid molecules with specific sequences matching theoligonucleotide are trapped on the surface of the solid and detected.

This kind of isolation and detection method, in which biological probesare immobilized on the surface of a solid and hybridization proceedsbetween the probes and a sample, has long been known as a blottingmethod in which the presence of the target molecule is detected by aprobe immobilized on a membrane using radioactive labeling. However,immobilization of a large number of probes on a small area has theadvantage that only a small amount of sample is required, and a largenumber of probes can be used simultaneously.

There are several methods for production of such products. Probemolecules can be synthesized one base at a time by a photochemicalreaction on small segments of a solid using the same photomaskingtechniques used in the semiconductor industry. In another method, asynthesized DNA, a PCR-amplified DNA, or a protein molecule isimmobilized on a small segment of the surface of a solid for each probe.A third method is to use an inkjet droplet to deposit the biologicalprobe onto the surface. After the biological probes are attached to thesurface, the sample containing the target molecule to be analyzed ispassed over the biological probes at a temperature conducive to rapidhybridization of the target molecule with the probes. A washing solutionthen removes all the unhybridized, unbound molecules.

This method requires the use of fluorescent or radioactive labels asadditional materials. Such a system is expensive to use and is notamenable to being made portable for biological sample detection andidentification. Furthermore, the hybridization reactions can take up totwo hours, which for many uses, such as detecting biological warfareagents, is simply too long. Therefore, a need exists for a device andsystem which can rapidly detect target molecules from samples.

The present invention is directed to achieving these objectives.

SUMMARY OF THE INVENTION

The present invention relates to a method of manufacturing a detectiondevice. The method first involves providing a substrate having a layerof aluminum between a first layer of photosensitive material and a baselayer. Next, the substrate is subjected to a first levelphotolithography treatment to produce an aluminum electrical conductorcontaining conductive fingers with spaces between them. The spacesbetween the conductive fingers are covered with an electrical insulatormaterial. Finally, biological probes are attached to the conductivefingers under conditions effective to form a gap between the biologicalprobes on the spaced apart conductive fingers, where a target molecule,if present in a sample, can bind to a pair of the biological probes onthe spaced apart conductive fingers. This bridges the gap between thebiological probes, allowing detection of the target molecule.

Another aspect of the present invention relates to a method ofmanufacturing a detection device, which first involves providing asubstrate having a base layer. Next, a first layer of electricalinsulator material is deposited on one side of the base layer. A layerof aluminum is deposited on the first layer of electrical insulatormaterial. Next, a first layer of photosensitive material is then coatedonto the layer of aluminum. Certain portions of the first layer ofphotosensitive material are exposed to ultraviolet light through a firstphotomask, and the first layer of photosensitive material is developedand baked, leaving portions of the layer of aluminum uncovered. Then,the uncovered portions of the layer of aluminum are removed from thesubstrate, leaving portions of the first layer of electrical insulatormaterial uncovered. Next, the photosensitive material remaining on thelayer of aluminum is removed. Then, a diamond film is deposited on thesubstrate, and a second layer of photosensitive material is coated ontothe diamond film. Next, the second layer of photosensitive material isexposed to ultraviolet light through a second photomask, and the secondlayer of photosensitive material is developed and baked, leavingportions of the diamond film uncovered. Then, the uncovered portions ofthe diamond film are removed from the layer of aluminum, where theexposing the second layer of photosensitive material, the developing andbaking the second layer of photosensitive material, and the removing theuncovered portions of the diamond film are carried out such that onlyportions of the diamond film aligned with the conductive fingers will beremoved, leaving portions of the second layer of photosensitive materialon the substrate. Next, the second layer of photosensitive materialremaining on the diamond film is removed. Finally, biological probes areattached to the conductive fingers under conditions effective to form agap between the biological probes on the spaced apart conductivefingers, As a result, a target molecule, if present in a sample, canbind to a pair of the biological probes on the spaced apart conductivefingers to bridge the gap between the biological probes, allowingdetection of the target molecule.

The present invention also relates to a method of manufacturing adetection device, which involves providing a substrate having analuminum electrical conductor containing a plurality of coplanarconductive fingers with spaces between them, where the spaces arecovered with an electrical insulator material. Biological probes arethen attached to the conductive fingers under conditions effective toform a gap between probes on the spaced apart, coplanar, conductivefingers. As a result, a target molecule, if present in a sample, canbind to a pair of the biological probes on the spaced apart, coplanar,conductive fingers to bridge the gap between the biological probes,allowing detection of the target molecule.

Another aspect of the present invention relates to a method ofmanufacturing a detection device. The method first involves providing asubstrate having a layer of aluminum and a first layer of photosensitivematerial. Then, the substrate is subjected to a first levelphotolithography treatment to produce an aluminum electrical conductorhaving conductive fingers with spaces between them. Finally, biologicalprobes are attached to the conductive fingers under conditions effectiveto form a gap between the biological probes on the spaced apartconductive fingers. As a result, a target molecule, if present in asample, can bind to a pair of the biological probes on the spaced apartconductive fingers to bridge the gap between the biological probes,allowing detection of the target molecule.

The present invention provides methods of fabricating a device forrapidly detecting the presence of biological material. The targetmolecule either itself or as a support is used to complete an electricalcircuit. The presence of the target molecule is indicated by the abilityto conduct an electrical signal through the circuit. In the case wherethe target molecule is not present, the circuit will not be completed.Thus, the target molecule acts as a switch. The presence of the targetmolecule provides an “on” signal for an electrical circuit, whereas thelack of the target molecule is interpreted as an “off” signal. Due tothe direct detection of the target molecule, the device allows forextremely sensitive detection of target molecules connecting twoelectrical conductors.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-P illustrate the sequence of steps necessary for fabricating adevice for detecting the presence of a target molecule. FIG. 1A depictsthe cross sectional view of a substrate having a base layer. FIG. 1B isa cross sectional view of a substrate where a first layer of electricalinsulator material has been deposited on one side of the base layershown in FIG. 1A. FIG. 1C illustrates the cross sectional view of asubstrate where a layer of aluminum has been deposited on the firstlayer of electrical insulator material shown in FIG. 1B. FIG. 1D depictsthe cross sectional view of a substrate where a first layer ofphotosensitive material has been coated onto the layer of aluminum shownin FIG. 1C. FIG. 1E shows the cross sectional view of a substrate wherecertain portions of the first layer of photosensitive material shown inFIG. 1D are exposed to ultraviolet light through a first photomask. FIG.1F is a cross sectional view of a substrate where the first layer ofphotosensitive material shown in FIG. 1E has been developed and baked,leaving portions of the layer of aluminum uncovered. FIG. 1G illustratesthe cross sectional view of a substrate where the uncovered portions ofthe layer of aluminum shown in FIG. 1F has been removed, leavingportions of the first layer of electrical insulator material uncovered.FIG. 1H is a cross sectional view of a substrate where thephotosensitive material remaining on the layer of aluminum shown in FIG.1G has been removed. FIG. 1I shows the cross sectional view of asubstrate where a diamond film has been deposited on the substrate shownin FIG. 1H. FIG. 1J illustrates the cross sectional view of a substratewhere a second layer of photosensitive material has been coated onto thediamond film shown in FIG. 1I. FIG. 1K depicts the cross sectional viewof a substrate where the second layer of photosensitive material shownin FIG. 1J is being exposed to ultraviolet light through a secondphotomask. FIG. 1L is a cross sectional view of a substrate where thesecond layer of photosensitive material shown in FIG. 1K has beendeveloped and baked, leaving portions of the diamond film uncovered.FIG. 1M shows the cross sectional view of a substrate where theuncovered portions of the diamond film have been removed from the layerof aluminum, leaving portions of the second layer of photosensitivematerial on the substrate. FIG. 1N illustrates the cross sectional viewof a substrate where the second layer of photosensitive materialremaining on the diamond film shown in FIG. 1M has been removed. FIG. 1Odepicts the top view of the fabricated device before the biologicalprobes are attached. FIG. 1P shows the top view of the fabricated deviceafter the biological probes are attached.

FIG. 2A illustrates an embodiment of the present invention whereoligonucleotide probes are attached to the spaced part conductivefingers of the fabricated device shown in FIG. 1P. FIG. 2B shows how atarget nucleic acid molecule present in a sample is detected by thefabricated device shown in FIG. 1P.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a method of manufacturing a detectiondevice. The method first involves providing a substrate having a layerof aluminum between a first layer of photosensitive material and a baselayer. Next, the substrate is subjected to a first levelphotolithography treatment to produce an aluminum electrical conductorcontaining conductive fingers with spaces between them. The spacesbetween the conductive fingers are covered with an electrical insulatormaterial. Finally, biological probes are attached to the conductivefingers under conditions effective to form a gap between the biologicalprobes on the spaced apart conductive fingers, where a target molecule,if present in a sample, can bind to a pair of the biological probes onthe spaced apart conductive fingers. This bridges the gap between thebiological probes, allowing detection of the target molecule.

Another aspect of the present invention relates to a method ofmanufacturing a detection device, which first involves providing asubstrate having a base layer. Next, a first layer of electricalinsulator material is deposited on one side of the base layer. A layerof aluminum is deposited on the first layer of electrical insulatormaterial. Next, a first layer of photosensitive material is then coatedonto the layer of aluminum. Certain portions of the first layer ofphotosensitive material are exposed to ultraviolet light through a firstphotomask, and the first layer of photosensitive material is developedand baked, leaving portions of the layer of aluminum uncovered. Then,the uncovered portions of the layer of aluminum are removed from thesubstrate, leaving portions of the first layer of electrical insulatormaterial uncovered. Next, the photosensitive material remaining on thelayer of aluminum is removed. Then, a diamond film is deposited on thesubstrate, and a second layer of photosensitive material is coated ontothe diamond film. Next, the second layer of photosensitive material isexposed to ultraviolet light through a second photomask, and the secondlayer of photosensitive material is developed and baked, leavingportions of the diamond film uncovered. Then, the uncovered portions ofthe diamond film are removed from the layer of aluminum, where theexposing the second layer of photosensitive material, the developing andbaking the second layer of photosensitive material, and the removing theuncovered portions of the diamond film are carried out such that onlyportions of the diamond film aligned with the conductive fingers will beremoved, leaving portions of the second layer of photosensitive materialon the substrate. Next, the second layer of photosensitive materialremaining on the diamond film is removed. Finally, biological probes areattached to the conductive fingers under conditions effective to form agap between the biological probes on the spaced apart conductivefingers. As a result, a target molecule, if present in a sample, canbind to a pair of the biological probes on the spaced apart conductivefingers to bridge the gap between the biological probes, allowingdetection of the target molecule.

The present invention also relates to a method of manufacturing adetection device, which involves providing a substrate having analuminum electrical conductor containing a plurality of coplanarconductive fingers with spaces between them, where the spaces arecovered with an electrical insulator material. Biological probes arethen attached to the conductive fingers under conditions effective toform a gap between probes on the spaced apart, coplanar, conductivefingers. As a result, a target molecule, if present in a sample, canbind to a pair of the biological probes on the spaced apart, coplanar,conductive fingers to bridge the gap between the biological probes,allowing detection of the target molecule.

Another aspect of the present invention relates to a method ofmanufacturing a detection device. The method first involves providing asubstrate having a layer of aluminum and a first layer of photosensitivematerial. Then, the substrate is subjected to a first levelphotolithography treatment to produce an aluminum electrical conductorhaving conductive fingers with spaces between them. Finally, biologicalprobes are attached to the conductive fingers under conditions effectiveto form a gap between the biological probes on the spaced apartconductive fingers. As a result, a target molecule, if present in asample, can bind to a pair of the biological probes on the spaced apartconductive fingers to bridge the gap between the biological probes,allowing detection of the target molecule.

One embodiment of the method of the present invention is set forth inFIGS. 1A-P which depict the sequence of steps necessary for fabricatinga device for detecting the presence of a target molecule.

This method first involves providing a substrate having base layer 2, asshown in FIG. 1A. An example of a suitable base layer material issilicon.

First layer of electrical insulator material 4 is deposited on one sideof base layer 2, as shown in FIG. 1B. Examples of useful electricalinsulator materials include silicon hard coat, silicon nitride, silicondioxide, and polyimide.

Layer of aluminum 6, an electrically conductive material, is depositedon first layer of electrical insulator material 4, as shown in FIG. 1C.

First layer of photosensitive material 8 is coated onto layer ofaluminum 6, as shown in FIG. 1D. Various photoresists, which areselected depending upon the exposing wavelength, can be used for thispurpose.

Certain portions of first layer of photosensitive material 8 are exposedto ultraviolet light 10 through first photomask 12, as shown in FIG. 1E.Lithographic techniques used in the semiconductor manufacturingindustries, such as photolithographic etching, plasma etching, or wetchemical etching, can be employed in the present invention.Alternatively, micromachining methods, such as laser drilling,micromilling and the like can be utilized.

First layer of photosensitive material 8 is developed and baked, leavingportions of layer of aluminum 6 uncovered, as shown in FIG. 1F. Suchdevelopment and baling is carried out by developing the exposedsubstrate in a base developer and hard baking on a hot plate.

Uncovered portions of layer of aluminum 6 are removed from thesubstrate, leaving portions of first layer of electrical insulatormaterial 4 uncovered, as shown in FIG. 1G. Layer of aluminum 6 isremoved by etching the substrate with an aluminum etchant.

Photosensitive material 8 remaining on layer of aluminum 6 is removed,as shown in FIG. 1H. This step can be carried out by using acetone. Inone embodiment, portions of the first layer of photosensitive materialthat were exposed to ultraviolet light are removed. Alternatively, thisstep can be carried out such that the portions of the first layer ofphotosensitive material that were not exposed to ultraviolet light areremoved.

Next, diamond film 14, an electrical insulator material, is deposited onthe substrate, as shown in FIG. 1I.

Second layer of photosensitive material 16 is coated onto the diamondfilm 14, as shown in FIG. 1J. Various photoresists, which are selecteddepending upon the exposing wavelength, can be used for this purpose.

Second layer of photosensitive material 16 is exposed to ultravioletlight 10 through a second photomask 18, as shown in FIG. 1K.

Exposed second layer of photosensitive material 16 is developed andbaked, leaving portions of diamond film 14 uncovered, as shown in FIG.1L. Such development and baking is carried out by developing the exposedsubstrate in a base developer and hard baking on a hot plate.

As shown in FIG. 1M, the uncovered portions of diamond film 14 areremoved from layer of aluminum 6. This is carried out by plasma etchingin O₂. Only portions of diamond film 14 aligned with the conductivefingers are removed. Portions of second layer of photosensitive material16 are left on the substrate, as shown in FIG. 1M.

Second layer of photosensitive material remaining 16 on diamond film 14is removed, as shown in FIG. 1N. This step can be carried out by usingacetone. In one embodiment, portions of the second layer ofphotosensitive material that were exposed to ultraviolet light areremoved. Alternatively, this step can be carried out such that theportions of the second layer of photosensitive material that were notexposed to ultraviolet light are removed.

The top view of the final fabricated device with two contact cuts 20 andan active area with spaced apart conductive fingers 22 exposed is shownin FIG. 10.

Finally, biological probes 24 are attached to conductive fingers 22under conditions effective to form a gap between biological probes 24 onspaced apart conductive fingers 22, as shown in FIG. 1P. As a result, atarget molecule, if present in a sample, can bind to a pair of thebiological probes on the spaced apart conductive fingers to bridge thegap between the biological probes, allowing detection of the targetmolecule. Details on methods of attaching biological molecules toelectrically conductive surfaces can be found in U.S. Provisional PatentApplication Serial No. 60/310,937, filed on Aug. 8, 2001, which ishereby incorporated by reference in its entirety.

In one embodiment of the present invention, the biological probes areproteins or antibodies. FIG. 2 shows another embodiment of the presentinvention where the biological probes are oligonucleotide probes and thetarget molecule is a nucleic acid molecule. The oligonucleotide probescan be in the form of DNA, RNA, or protein nucleotide analogues. Sucholigonucleotide probes are advantageously constructed from about 10 to30 nucleotide bases. Shorter probe molecules have lower specificity fora target molecule, because there may exist in nature more than onetarget nucleic acid molecule with a sequence of nucleotidescomplementary to a shorter probe molecule. On the other hand, longerprobe molecules have decreasingly small probabilities of complementarysequences with more than one natural target nucleic acid molecule. Inaddition, longer probe molecules exhibit longer hybridization times thanshorter probe molecules. Since analysis time is a factor in a commercialdevice, the shortest possible probe that is sufficiently specific to thetarget nucleic acid molecule is desirable. Both the speed andspecificity of binding target nucleic acid molecule to probe moleculescan be increased if one electrical conductor has attached a probemolecule that is complementary to one end of the target nucleic acidmolecule and the other electrical conductor has attached a probe that iscomplementary to the other end of the target nucleic acid molecule. Inthis case, even if short probe molecules that exhibit rapidhybridization rates are used, the specificity of the target molecule tothe two probes is high.

The fabricated device of the present invention is used to detect targetmolecules from samples. As shown in FIG. 2A, oligonucleotide probes 26attached to the spaced apart conductive fingers 22 are physicallylocated at a distance sufficient that they cannot come into contact withone another. A sample, containing a mixture of nucleic acid molecules(i.e. M1-M6), to be tested is contacted with the fabricated device onwhich conductive fingers 22 are fixed, as shown in FIG. 2B. If a targetnucleic acid molecule (i.e. M1) which is capable of binding to the twooligonucleotide probes is present in the sample, the target nucleic acidmolecule can electrically connect the two probes. Any unhybridizednucleic acid molecules (i.e. M2-M6) not captured by the probes is washedaway. Here, the electrical conductivity of nucleic acid molecules isrelied upon to transmit the electrical signal. Hans-Werner Fink andChristian Schoenenberger reported in Nature ( 1999 ), which is herebyincorporated by reference in its entirety, that DNA conducts electricitylike a semiconductor. This flow of current can be sufficient toconstruct a simple switch, which will indicate whether or not a targetnucleic acid molecule is present within a sample. The presence of atarget molecule can be detected as an “on” switch, while a set of probesnot connected by a target molecule would be an “off” switch. Theinformation can be processed by a digital computer which correlates thestatus of the switch with the presence of a particular target. Theinformation can be quickly identified to the user as indicating thepresence or absence of the biological material, organism, mutation, orother target of interest.

Optionally, after hybridization of the target molecules to sets ofbiological probes, the target molecule can be coated with a conductor,such as a metal, as described in U.S. patent application Ser. Nos.60/095,096 or 60/099,506, which are hereby incorporated by reference intheir entirety. The coated target molecule can then conduct electricityacross the gap between the pair of probes, thus producing a detectablesignal indicative of the presence of a target molecule.

EXAMPLES

The following examples are provided to illustrate embodiments of thepresent invention but are by no means intended to limit its scope.

Example 1 Fabrication of a Detection Device with Aluminum ElectricalConductors

Fabrication began with a bare 6″ silicon wafer (n-type or p-type) with(100) orientation, a resistivity of 5-15 ohm·cm, and a thickness of675+50 μm.

A layer of silicon hard coat, as a first electrical insulator layer, wasspin-coated on one side of the silicon wafer. A puddle of silicon hardcoat (methylsilsesquioxane solution; SHC1200, GE Silicones, Waterford,N.Y.), about 3 inches in diameter, was dispensed onto the wafer, whichwas then spun at 3000 rpm for 180 sec.

A layer of aluminum was either sputtered or evaporated to the desiredthickness onto the layer of silicon hard coat. When sputtered, power wasset at 2000 Watts, argon flow at 63 sccm, presputter time at 5 min,chamber pressure at 106 Torr, deposition pressure at 5 mTorr, anddeposition rate at 240 A/min. Alternatively, an aluminum pellet wasevaporated using the evaporator (CVC, Port Townsend, Wash.) set at anappropriate chamber pressure (low 10⁻⁶ Torr) to give an approximatethickness of 2000 Å.

A first layer of photoresist was coated onto the aluminum layer. Thewafer was coated using coat trac or was hand-coated using Oir 620, apositive photoresist containing novalac resin, diazonaphthoquinone,casting solvent, additives, and surfactants (Olin, Norwalk, Conn.). Whenhand-coating, the substrate must be dehydration baked at 200° C. for 2min on a hot plate, the photoresist must be dispensed at 4500 rpm for 1min, and the substrate must be soft baked at 90° C. for 1 min on a hotplate.

The substrate was subjected to a first level lithography treatment,using an i-line stepper (Canon, Japan). The stepper job was loaded usingthe command, “ST DNA3_level 1.” The exposure dose was set at 130 mj/cm².

The exposed wafer was developed in a base developer (Shipley CD26,Shipley, Marboro, Mass.) for 1 min and rinsed with water. The wafer wasdried and hard baked on a hot plate at 120° C. for 2 min.

The exposed aluminum was removed by etching the wafer with aluminumetchant at 50° C., and rinsing well in DI water. The etching timedepended on the thickness of aluminum, and the etch rate was 2000 Å/min.

The photoresist remaining on the aluminum layer was removed with acetoneand rinsed with DI water.

A diamond film, as a second electrical insulator layer, was spin-coatedonto the substrate.

The substrate was then coated with photoresist as previously described.

The substrate was subjected to a second level lithography treatment toopen active areas and contact cuts, using an i-line stepper (Canon,Japan). The stepper job was loaded using the command, “ST DNA3_level 1.”The substrate was exposed and a post-exposure bake was performed asdescribed for the first level lithography. An exposure dose of 130mj/cm² was used.

The exposed substrate was developed in the base developer for 1 min andrinsed with water. Then, the substrate was dried and hard baked on a hotplate at 120° C. for 2 min.

Next, the exposed diamond film was removed by plasma etching in O₂. Thisstep is not necessary if photoresist is used as the second electricalinsulator layer.

Next, the photoresist remaining on the aluminum layer was removed withacetone. This step is not necessary if photoresist is used as the secondelectrical insulator layer.

Finally, biological probe molecules are attached to the active area ofthe fabricated device with the aluminum electrical conductors exposed.

Although the invention has been described in detail for the purpose ofillustration, it is understood that such detail is solely for thatpurpose, and variations can be made therein by those skilled in the artwithout departing from the spirit and scope of the invention which isdefined by the following claims.

1. A method of manufacturing a detection device, said method comprising:providing a substrate having a layer of aluminum between a first layerof photosensitive material and a base layer; subjecting the substrate toa first level photolithography treatment to produce an aluminumelectrical conductor comprising conductive fingers with spaces betweenthem; covering the spaces between the conductive fingers with anelectrical insulator material; and attaching biological probes to theconductive fingers under conditions effective to form a gap between thebiological probes on the spaced apart conductive fingers, whereby atarget molecule, if present in a sample, can bind to a pair of thebiological probes on the spaced apart conductive fingers to bridge thegap between the biological probes, allowing detection of the targetmolecule.
 2. A method according to claim 1, wherein the biologicalprobes are oligonucleotide probes and the target molecule is a nucleicacid molecule.
 3. A method according to claim 1, wherein the biologicalprobes are proteins or antibodies.
 4. A method according to claim 1,wherein said substrate further comprises a first layer of electricalinsulator material between the base layer and the layer of aluminum. 5.A method according to claim 4, wherein said providing a substratecomprises: depositing the first layer of electrical insulator materialon one side of the base layer; depositing the layer of aluminum on thefirst layer of electrical insulator material; and coating the firstlayer of photosensitive material onto the layer of aluminum.
 6. A methodaccording to claim 4, wherein said subjecting the substrate to firstlevel photolithography treatment comprises: exposing certain portions ofthe first layer of photosensitive material to ultraviolet light througha first photomask; developing and baking the first layer ofphotosensitive material leaving portions of the layer of aluminumuncovered; removing the uncovered portions of the layer of aluminum fromsaid substrate, leaving portions of the first layer of electricalinsulator material uncovered; and removing the photosensitive materialremaining on the layer of aluminum.
 7. A method according to claim 6,wherein said method is carried out such that the portions of the firstlayer of photosensitive material that were exposed to ultraviolet lightare removed.
 8. A method according to claim 6, wherein said method iscarried out such that the portions of the first layer of photosensitivematerial that were not exposed to ultraviolet light are removed.
 9. Amethod according to claim 1, wherein said covering the spaces betweenthe conductive fingers with an electrical insulator material comprises:depositing a diamond film on said substrate after said subjecting thesubstrate to a first level photolithography treatment; coating a secondlayer of photosensitive material onto the diamond film; and subjectingthe substrate to a second level photolithography treatment to cover thespaces between the conductor fingers with the diamond film.
 10. A methodaccording to claim 9, wherein said subjecting the substrate to a secondlevel photolithography treatment comprises: exposing the second layer ofphotosensitive material to ultraviolet light through a second photomask;developing and baking the second layer of photosensitive material,leaving portions of the diamond film uncovered; removing the uncoveredportions of the diamond film from said layer of aluminum, wherein saidexposing, said developing and baking, and said removing the uncoveredportions of the diamond film during said second level photolithographytreatment are carried out such that only portions of the diamond filmaligned with the conductive fingers will be removed, leaving portions ofthe second layer of photosensitive material on the substrate; andremoving the second layer of photosensitive material remaining on thediamond film.
 11. A method according to claim 10, wherein said method iscarried out such that the portions of the second layer of photosensitivematerial that were exposed to ultraviolet light are removed.
 12. Amethod according to claim 10, wherein said method is carried out suchthat the portions of the second layer of photosensitive material thatwere not exposed to ultraviolet light are removed.
 13. A methodaccording to claim 1, wherein the electrical insulator material coveringthe spaces between the conductive fingers is a diamond film.
 14. Amethod of manufacturing a detection device, said method comprising:providing a substrate having a base layer, depositing a first layer ofelectrical insulator material on one side of the base layer; depositinga layer of aluminum on the first layer of electrical insulator material;coating a first layer of photosensitive material onto the layer ofaluminum; exposing certain portions of the first layer of photosensitivematerial to ultraviolet light through a first photomask; developing andbaking the first layer of photosensitive material, leaving portions ofthe layer of aluminum uncovered; removing the uncovered portions of thelayer of aluminum from said substrate, leaving portions of the firstlayer of electrical insulator material uncovered; removing thephotosensitive material remaining on the layer of aluminum; depositing adiamond film on said substrate; coating a second layer of photosensitivematerial onto the diamond film; exposing the second layer ofphotosensitive material to ultraviolet light through a second photomask;developing and baking the second layer of photosensitive material,leaving portions of the diamond film uncovered; removing the uncoveredportions of the diamond film from said layer of aluminum, wherein saidexposing the second layer of photosensitive material, said developingand baking the second layer of photosensitive material, and saidremoving the uncovered portions of the diamond film are carried out suchthat only portions of the diamond film aligned with the conductivefingers will be removed, leaving portions of the second layer ofphotosensitive material on the substrate; and removing the second layerof photosensitive material remaining on the diamond film; and attachingbiological probes to the conductive fingers under conditions effectiveto form a gap between the biological probes on the spaced apartconductive fingers, whereby a target molecule, if present in a sample,can bind to a pair of the biological probes on the spaced apartconductive fingers to bridge the gap between the biological probes,allowing detection of the target molecule.
 15. A method according toclaim 14, wherein the biological probes are oligonucleotide probes andthe target molecule is a nucleic acid molecule.
 16. A method accordingto claim 14, wherein the biological probes are proteins or antibodies.17. A method according to claim 14, wherein said method is carried outsuch that the portions of the first layer of photosensitive materialthat were exposed to ultraviolet light are removed.
 18. A methodaccording to claim 14, wherein said method is carried out such that theportions of the first layer of photosensitive material that were notexposed to ultraviolet light are removed.
 19. A method according toclaim 14, wherein said method is carried out such that the portions ofthe second layer of photosensitive material that were exposed toultraviolet light are removed.
 20. A method according to claim 14,wherein said method is carried out such that the portions of the secondlayer of photosensitive material that were not exposed to ultravioletlight are removed.
 21. A method of manufacturing a detection device,said method comprising: providing a substrate having an aluminumelectrical conductor comprising a plurality of coplanar conductivefingers with spaces between them, wherein the spaces are covered with anelectrical insulator material; and attaching biological probes to theconductive fingers under conditions effective to form a gap betweenprobes on the spaced apart, coplanar, conductive fingers, whereby atarget molecule, if present in a sample, can bind to a pair of thebiological probes on the spaced apart, coplanar, conductive fingers tobridge the gap between the biological probes, allowing detection of thetarget molecule.
 22. A method according to claim 21, wherein thebiological probes are oligonucleotide probes and the target molecule isa nucleic acid molecule.
 23. A method according to claim 21, wherein thebiological probes are proteins or antibodies.
 24. A method according toclaim 21, wherein the electrical insulator material covering the spacesbetween the conductive fingers is a diamond film.
 25. A method ofmanufacturing a detection device, said method comprising: providing asubstrate having a layer of aluminum and a first layer of photosensitivematerial; subjecting the substrate to a first level photolithographytreatment to produce an aluminum electrical conductor comprisingconductive fingers with spaces between them; and attaching biologicalprobes to the conductive fingers under conditions effective to form agap between the biological probes on the spaced apart conductivefingers, whereby a target molecule, if present in a sample, can bind toa pair of the biological probes on the spaced apart conductive fingersto bridge the gap between the biological probes, allowing detection ofthe target molecule.
 26. A method according to claim 25, wherein saidsubstrate further comprises a base layer wherein said layer of aluminumis between said first layer of photosensitive material and said baselayer.
 27. A method according to claim 25, further comprising: coveringthe spaces between the conductive fingers with an electrical insulatormaterial, prior to said attaching biological probes and after saidsubjecting the substrate to a first level photolithography.
 28. A methodaccording to claim 27, wherein the electrical insulator materialcovering the spaces between the conductive fingers is a diamond film.29. A method according to claim 25, wherein the biological probes areoligonucleotide probes and the target molecule is a nucleic acidmolecule.
 30. A method according to claim 25, wherein the biologicalprobes are proteins or antibodies.